Hot flashes affect approximately 75% of postmenopausal women. Although hormone replacement therapy (HRT) is highly effective in reducing hot flashes, long-term HRT is associated with increased rates of breast cancer and heart disease. Safe, effective, and well-tolerated hot flash alternative therapies are needed. We have shown the anticonvulsant gabapentin to be effective in the treatment of hot flashes in postmenopausal women; however, 50% of patients receiving gabapentin reported side effects of sleepiness or dizziness. Gabapentin is known to bind to the alpha2delta subunit of voltage-gated calcium channels (VGCCs) in the central nervous system (CNS). The amino acids L-methionine and L-norleucine also bind to the alpha2delta subunit with high affinity. Recently, we have noted a 75-100% reduction in hot flash frequency among 5 women after initiating either open-label oral L-methionine or L-norleucine therapy. Long-term L-methionine therapy may carry increased cardiovascular risks by increasing serum homocysteine levels while L-norleucine therapy will not increase homocysteine levels. Over the 5-year career development award, the applicant will principally pursue clinical research examining the safety, tolerability, and efficacy of L-norleucine therapy in hot flash treatment. The clinical research will be performed in the University's General Clinical Research Center under the mentorship of Drs. Kieburtz and Guzick. In addition to this clinical work, the applicant will concurrently pursue basic science training in the laboratory of co mentor Dr. Richfield on better elucidating the mechanism of action of L-norleucine therapy in the treatment of hot flashes and on optimizing future hot flash therapies. Direct mentored training will occur throughout the 5-year award. The applicant will participate in one clinical research meeting and one basic science journal club meeting every week. In addition, formal didactic training in epidemiology and neuroscience will occur at the University. The applicant will also attend two didactic training seminars in complementary & alternative medicine at The Osher Institute at Harvard Medical School and at the Duke Center for Integrative Medicine.